The Black Death

Question 1

Describe the modes of transmission of the plague

Answer 1

1. Flea bite
2. Inhalation from humans or animals - pneumonic
3. Handling infected animals (contact, scratches, bites)
4. Ingesting infected meat

Question 2

Describe the 3 major forms of the plague

Answer 2

1. Bubonic plague (most common)
   
   • Transmitted by flea bites
   • Buboes
   • Can develop into the other types
   • Untreated = 50% mortality
2. Septicemic plague
   
   • Bateria is systemic (bacteremia); their endotoxins cause symptoms
     
     • Gangrene (tissue death), disseminated intravascular coagulation (DIC - blood clots develop in blood stream)
   • Allows fleas to pick up bacteria
   • Untreated = 70% mortality
3. Pneumonic plague (most dangerous)
   
   • Transmitted via aerosols which enter directly into the lung (but may also develop from previous plagues)
     
     • No flea vector required
   • Coughing up blood
   • Untreated = 95% mortality - must be treated immediately

Question 3

Describe the first pandemic: the plague of Justinian (500 AD)

Answer 3

• Roman emperor Justinian
• Spread to through Europe killing 50% of population, 100 million people
  
  • Cycles in and out until 750 AD, likely related to immunity –> disappearence –> lack of immunity

Question 4

Describe the second pandemic: the black death (1300s)

Answer 4

• Originated in Asia, reached Europe, killed 1/3 of Europe, also 100 mil
• Strangers, minorities persecuted believed to be witches, devils, etc
• Breakdown of European Feudal System; allowed people to move up
  
  • Plague doctors: usually not real physicians; had flowers and herbs in their “beaks” for “protection”

Question 5

Describe the third pandemic (19th century)

Answer 5

• Active until 1960s
• >12 mil deaths in China, India, reached North America via rats on ships which exchanged fleas with local wildlife

Question 6

Describe the Yersinia genus of bacteria and the 3 important species

Answer 6

• Gram negative, rod shaped
• 3 species are pathogenic to humans
  
  • Y. enterocolitica: causes “yersiniosis”, rare diarrhea and abdominal pain
  • Y. pseudotuberculosis: animal pathogen with tuberculosis-like symptoms, enteritis (inflammation of intestine) in humans
  • Y. pestis: causes the plague

Question 7

Describe the meaning of the name of Y. pestis

What is unsual about it?

Answer 7

• Yersinia - discovered by Alexandre Yersin in 1900
• Pestis - pestilence
• Quick death of host = poor colonizer

Question 8

How do we know Y. pestis causes the plague?

Answer 8

• East London black death plague = creation of huge plague pit
• Teeth of plague victims obtained
  
  • Bacteria in blood would become lodged in teeth
  • Teeth preserve the DNA! –> sequence Y. pestis
    
    • Justinian area had different strain

Question 9

Describe the flea transmission of Y. pestis

Answer 9

• Y. pestis lives in rodents, transmitted by fleas (zoonotic, flea vector)
• Transmission
  
  1. Flea bites infected rat
  2. Bacteria grows in flea, forms biofilm blocking the proventriculus
     
     • Causes flea to starve; no nourishment from meals despite feeding
     • Starving flea = rapid biting = fast transmission

Question 10

Describe the infection path of Y. pestis

Answer 10

• Infection (infective dose is low, ~10 cells)
  
  • Y. pestis initially survives and grows in innate immune cells
    
    • Therefore it is an intracellular bacteria
  • Moves to lymphoid organs and replicates –> buboes
  • Terminal stage: kills phagocytes and grows extracellularly
    
    • Massive growth; can be picked up by flea to continue cycle

Question 11

Describe the virulence factors of Y. pestis

Answer 11

1. Gram negative = lipopolysaccharide endotoxin which is important for septicemia
2. Phospholipase breaks down phospholipids
3. Plasminogen activator activates plasminogen –> break open clots –> dissemination
4. Yersiniabactin binds iron = growth = increase virulence (level 3 to level 2 without iron)
5. Type 3 secretion system
   
   • Unique to intracellular Gram negatives
   • Secrete effectors (viruelence factors) directly into host cell like a syringe
     
     • Poison host cell by targeting signalling pathways

Question 12

Describe the evolution of Y. pestis

Answer 12

1. Non-pathogenic Yersinia acquires virulence plasmid pYV which encodes type 3 secretion system –> pathogen
2. Acquires genes for biofilm formation, insect toxin –> animal and intestinal pathogen
3. The strain acquires 2 plasmids; loses genes related to instestine
   
   1. Phospholipase –> survival in flea
   2. Plasminogen activator –> dissemination

Question 13

Describe the diagnosis and treatment of the plague, as well as prevention

Answer 13

• Rapid diagnosis and treatment with ABx
• Culture and identification from bubo aspirate, sputum (mucus/spit), or blood (post mortem) may take 4 days
• More rapid tests include stains and antigen tests

Prevention (i.e. prophylaxis) includes isolation of and treating infected, killing fleas

Question 14

How can Y. pestis be effective as a bioterrorism agent?

Answer 14

• CDC identifies plague as category A organism
  
  • Easily disseminated/transmitted
  • High mortality
  • Social breakdown, panic
• Easy to grow (2 days)
• Used in the past
  
  • Mongolian armies, WWII japanese

Question 15

What is the modern plague like?

Answer 15

• Not found in Australia
• Recent outbreak of pneumonic in Madagascar
• Widespread in wildlife rodent reservoirs